Halogeno-carboxylic amides



Patented July 28, 1942 UNITED STATES PATENT OFFICE HALOGEN O-GARBOXYLICAMIDES Morris B. Katzman, Chicago, Ill., assignor to The EmulsolCorporation, Chicago, 111., a corporation of Illinois No Drawing.Application July 22, 1940,

Serial No. 346,806

20 Claims.

posses some properties which adapt them, as

such, for use for the purposes indicated above.

At least most of the novel compounds fall within the scope of thegeneral formula:

RO( TNY) mCOZ-halw wherein R. is an organic radical, preferablycontaining at least four carbon atoms, T stands for hydrocarbon, forexample, alkylene or arylene such as ethylene or phenylene, Y ishydrogen,

alkyl, cycloalkyl, alkoxyl, ar-alkyl, aryl, or alkylol,

Z is preferably hydrocarbon, containing preferably less than six carbonatoms, hal .is halogen, and m and w are .whole numbers, preferably fromone to four.

A more limitedaspect of the compounds of the invention may berepresented by the general formula wherein R is a hydrocarbon radical orsubstituted hydrocarbon radical containing at least seven and preferablyfrom eleven to seventeen carbon atoms, and hal is halogen.

The radical R in the above formula may be of aliphatic cycloaliphatic,aromatic or aromaticaliphatic character, and may contain substituentgroups such as amino, hydroxy, halogen, sulphate, sulphonic, phosphate,carboxyl, nitrile, and the'like, as will be pointed out hereinafter, butit. is particularly preferred that it be unsubstituted aliphatic orfatty and contain upwards of ten carbon atoms to about eighteen carbonatoms. Z and T, likewise, may contain substituent groups such as amino,hydroxy, halogen, sulphate, sulphonic, phosphate, carboxyl, nitrile, andthe like, and the sequence of carbon atoms therein may be interrupted byO, S, C=O, NH, NR, where R is alkyl, and the like.

In order that the nature of the invention may become more apparent,there are listed hereinbelow representative compounds which fall withinthe scope of the invention. It will be understood that such compoundsmay be utilized in the pure or impure state or in the :form of reactionmixtures containing predominant or substantial proportions of saidcompounds or in the form of mixtures of any two or more of saidcompounds. It will further be appreciated that the acyl groups, thehydroxy amine groups and the halogeno-carboxylic acid groups which enterinto the formation of the various compounds may be interchanged withoutdeparting from the spirit of the invention:

O 0 Cl (abietic acid) (249 CgHga-i'i-OONH-E-ClL-Cl tate, and 'lowtemperatures are employed, of the order of about -l degrees C to aboutdegrees C., excellent yields of amide are obtained. The resulting amideis then reacted with an organic acid or halide thereof, particularly ahigher molecular weight organic acid or halide thereof to produce theester. The process is preferably carried out in a non-aqueous medium,namely, one which is substantially devoid of water, this procedureproducing the best yields and resulting in other advantages renderingthe process more economical. By a non-aqueous medium is meant one whereeither the two reactants may be present or one of them may be insuspension ot halogeno-acetic acid, for example, methyl chloracetate aredecidedly superior to the corresponding ethyl esters for reaction withmonoethanolamine or similar non-tertiary alkylolamines to produce thehalogeno-acetamides of the monoethanolamine or the like. Furthermore,

' by operating at low temperatures of the character indicatedhereinabove, that is, preferably not substantially exceeding +10 degreesC., the undesired alkylation of the monoethanolamine or the like issubstantially avoided and far more complete amidification occurs withbetter yields of amide than is the case where the corresponding ethylalcohol esters are used as startin material. It is accordingly to beunderstood that the employment of the methyl alcohol esters of thehalogeno-acetic acids, under the conditions enumerated, represents adistinctly preferred and important phase of the present invention.

The following examples are illustrative of methods which have been foundsuitable for preparing various of the compounds which aredisclosed'herein. It will be appreciated that other methods may beutilized and that the proportions of reacting ingredients, times ofreaction, orderv of steps, and temperatures may be varied and thatsupplementary processes of purification and the like maybe resorted towherever found desirable or convenient. These and other variations andmodifications will be evident to those skilled in the art in the lightof the guiding principles which are disclosed herein.

Example A (1) 122 grams of ethyl chloracetate were added slowly to a 25%aqueous solution containing 122 grams of monoethanolamine, the reactionbeing conducted at a temperature of 0 degrees C. to 10 degrees C. At theend of 15 minutes the reaction appeared to be complete. Approximately126 rams of oxalic acid were then added to neutralize the excess ofethanolamine, maintaining preferably a temperature of 0 degrees C. to 10degrees C. The water present in the reaction mixture was then evaporatedoff onthe waterbath and 1000 grams of iso-propyl-alcohol were added. Themass was then filtered, the monoethanolamine oxalate being insoluble,and the alcohol was distilled off from the filtrate on a water bathunder vacuum. (The excess monoethanolamine may be removed, if desired,in any other manner as, for example, bydistillation under vacuum.) Theresulting product, consisting essentially of th N-beta-hydroxyethyl,chloracetamide, was a semi-viscous liquid.

(2) 14.8 grams of the N-beta-hydroxyethyl, chloracetamide, preparedasdescribed in part (1) hereof, and 18.8 grams of lauroyl. chloride werestirred vigorously while warming to 60 degrees C. over a period Of 10minutes. Approximately 5 minutes later, a vigorousreaction started withthe evolution of hydrochloric acid. The resulting product, namely, thelauric acid ester of N-beta-hydroxyethyl, chloracetamide, was a solid,soft, waxy material.

1 solved in 50 cc. of water and maintained in an ice'bath there wereadded dropwise, with vigorous stirring, 21.6 grams of alpha-brompropio'nyl bromide. When approximately half of the latter had beenadded, the dropwise addition of 46.5 cc. of 2N NaOH was begun, the restof the alphabrom propionyl bromide. being added dropwise meanwhile. Thereaction was completed in 15 minutes and the mass was then'evaporated onthe water bath. vIt was then extracted with 500 cc. of boiling isopropylalcohol and the mineral salts, such as sodium bromide, were filteredofi. The alcohol was then evaporated and the reaction product, which wasa viscous liquid, consisted essentially of a compound having the formulacm-cnco-Nn-m-omon r I (2) grams of the amide produced as described inpart 1 hereof and 8 grams of lauroyl chloride were heated together at 50degrees C.

c for approximately 5 minuteswith vigorous stir- ,ring. Whenhydrochloric acid was no longer evolved, the reaction was terminated.The resulting compound was the lauric acid ester of the amide producedin part 1 hereof.

Example C Example D (1) To 217 grams (2 mols) oimethyl chloracetate 62grams (1 mol) of inonoethanolamine were added slowly with stirrinmthetemperature of the mixture being kept at approximately 0 degrees C. Theaddition of themonoethanolamine was made over a period of about 1%hours, a small amount of finely divided solid carbon dioxide being addedtothe reaction product to help maintain the temperature at aboutO'degrees C. The reaction product was then sub- Jected to a vacuum at atemperature of '20 degrees C. to 50 degrees C. and at an absolutepressure or 12 mm.,to ,70 mm. in order to remove the methyl alcoholwhich formed during the reaction, the carbondioxide, and at least mostof the excess methyl chlor acetate. Approximately 180 grams of areaction product was obtainedconsisting essentially-of the chloracet-'(2) To' the reaction product of part l hereof,

330 grams of lauroyl chloride (approximatelyv a'cid which formed duringthe reaction. The reaction mass was then washed four, times with tapwater at 65 degrees C. until free of hydro-' chloricacid.

In the above example, it will be noted that the molal ratio of themethyl hlor acetate to the monoethanolamine was 2 to 1. Equal molalrader to obtain the best yields, ,to use an excess of methyl chloracetate. In general, a molal ratio of methyl chlor acetate tomonoethanolamine of about 1.5 to 1- to about 2 to 1 is preferred, thelatter molal ratio representing close to the optimum operatingconditions.

It should also be understood that the use of solid carbon dioxide may beomitted and, if desired, oxalic acid may be employed to precipitateexcess monoethanolamin should the reaction be carried out in such amanner that excess onoethanolamine is present. This, however,

oes not represent the preferred embodiment of the invention.-

Emample E (1) 108.5 grams of methyl chlor acetate were dissolved in 327grams of methyl alcohol and there were added thereto, slowly andwith'stir; ring, 74.4 grams of monoethanolamine. The reaction mixturewas maintained at a temperature of about. l0 degrees C. forapproximately 1% hours. The temperature was then allowed to rise over aperiod of about 1 hour to +10 degrees C. at which stage theamidification reaccomplete. The

tion was approximately 98% slight excess 01' monoethanolamine was thenremoved by adding slowly, and with stirring, 17.32 grams of oxalic aciddissolved in cc. of methyl alcohol. The precipitated oxalic acid salt ofmonoethanola'mine was-then filtered. oil and the methyl alcohol wasevaporated off under vacuum v utes and while maintaining the reactionmass at from the filtrate. At room temperature, the reaction product wasa viscous, pale straw to amber colored liquid and consisted essentiallyof the chloracetamide of monoethanolamine.

(2) 124 grams of the reaction product of part 1 hereof were mixed with176.5 grams of pure lauroylchloride and the mixture was heated, withstirring and under vacuum, for 1 hour at about 70 degrees C. until nomore hydrochloric acid was driven off. The reaction mass was then washedtwice, each time with 4 liters of water at 60 degrees C., until the washwater was free of hydrochloric acid.

In the above Example E, it will be noted that methyl alcohol is used asa diluent, the monoethanolamine'is employed in slight excess and theexcess thereof is removed by precipitation with oxalic acid.

- Example F ture for twelve hours. The methyl alcohol which formedduring the reaction and the excess methyl chloracetate were distilledoff in vacuo at atemperature of about .60 degrees C. The reactionproduct-contained a substantial proportion of the chloracetamide ofdiethanolamine.

(2) To 94 grams of the reaction product of part 1 hereof there wereadded dropwise and with stirring99 grams of lauroyl' chloride, theaddition being. made over a period of about 20 mina temperature rangingfrom 80 degrees C. to 100 degrees C. The final reaction product was atics may beemployed but it is preferred, in orclear, light amber,semi-viscous material containing a substantial proportion of a compoundhaving the following formula:-

' acetyl chloride. The temperature spontaneously rose from 26 to 68degrees p, hydrochloric acid gas being evolved. The reaction mixture wasthen permitted to cool to room temperature, the entire reaction timeamounting toabout 45 minutes. The product was a clear, semi-viscous,water-soluble, oilyliquid, comprising-largely the acetic acid ester ofthe chloracetamide of monopyridine carbqxylm; acids; hydmxy aromaticethanolamine.

. Example H 15 grams 01' the chloracetamide of mono ethanolamine and11.3 grams of chloracetyl chloride were mixed together'at roomtemperature, the temperature spontaneously rising to 85- degrees C. withvigorous evolution of HCl. On cooling to 55 degrees C., a clear yellowliquid was obtained and which was slightly watersoluble. It contained asubstantial proportion of the chloracetic acid ester of thechloracetamide of monoethanolamine.

It will be understood that the novel compounds of the present invention,set forth in the list herenabove,'may be produced in accordance with the5 processes-described or other processes which will be apparent to thoseskilled in the art in the light of my teachings herein. In thepreparation of specific compounds, it will, of course, be appre- -ciatedthat variations in proportions of the re- 40 actants, changesinjtemperature, and the like, may be advisable or necessary. However;such factors are well understood by those versed in the art and requireno elaboration.

It will be understood, particularly in the light of the exampleshereinabove, that the novel compounds of the present invention maycontain one or more imino or like linkages. Thus, for example, in placeof employing monoethanolamine or monopropanolamine 'or the like as astarting material, compounds may be utilized having a plurality of iminogroups such as the following, by way of illustration: a

The organic radical represented by R in'the general formulae may, asstated, be derived from various sources. Among such sources may bementioned straight chain and branched chain carboxylic, aliphatic, andfatty acids, saturated erucic acid, melissic acid, stearic acid, oleicaci 70 ricinoleic acid, linoleic acid, linolenic acid, lauric acid,myristic acid, palmitic acid, mixtures of any two or more of the abovementioned acids or other acids, mixed higher fatty acids derived fromanimal or vegetable sources, for example, 75

lard, coconut oil, rapeseed oil, sesameoiL'palm kernel oil,- palm oil,olive oil, corn oil, cottonseed 1o palrnitic acid, alpha-hydroxylauric'acid, alphahydroxy coconut oil mixed fatty acids, and the like;fatty acids derived from various waxes such as beeswax, spermac'eti,montan wax, and carnauba wax and carboxylic' acids derived, by 3oxidation and other methods, from petroleum;

cycloaliphatic and hydroaromatic acids such as hexahydrobenzoic acid,resinic acids, naphthenic acidand abietic acid; aromatic acids such asphthalic acid, benzoic acid, naphthoic acid,

example, the alpha-chlor fatty acid derivativesl such as chloracetylchloride, chlor butyryl chloride, chlorinated oleic acid, and the like.It'

will: be understood that mixtures of any two or more of said acids maybe employed if desired. Y

- In' those cases where ethersare prepared, the

organic, radical is derived from alcoholates of a1- cohols correspondingto the acids referred to hereinabove.

The halogeno-carboxylic acids which, in the form of their esters,particularly with methyl alcohol, are reacted with the primary andsecondary alcohol amines or alkylolamines may be selected from arelatively large class including mono-, di-, and poly-earboxylicderivatives as; for example, mono chloracetic acid, mono bromii aceticacid, mono iodo acetic acid, alpha-chlor propionic acid, alpha-brompropionic acid, alphachlor butyric acid, alpha-bromo calpric acid, monochlor succinic acid, di-chlor succinic acid, dichlor glutaric acid, andthe like; 0! special utility, as previously indicated, are methylalcohol esters of the halogeno acetic acids, particularly, methyl chloracetate.-

The alcohols whose halogeno-carboxylic esters are reacted with theprimary and secondary al-. cohol amines are preferably of lowermolecular weight, especially the volatile alcohols, namely, methylalcohol and ethyl alcohol, being preferred with the methyl alcohol beingespecially desirable when utilized under the conditions describedhereinabove. It will be understood that the reactivity of the alcoholesters of the halogenocarboxylic acids in connection with the forma-"tion of the amides therefrom with monoethanolamine or the likeisdependent uponthe alcohol portion of the ester molecule as well asupon the I halogeno-carboxylic acid with which it is esterifled. Ingeneral, the higher in the homologous and unsaturated, such as formicacid, acetic acid,

series of the alcohol and the halogeno-carboxylic acid, the lessreactive are the materials.

The primary andsecondary alcohol amines or alkylolamines, in otherwords, the non-tertiary alcohol amines and alkylolamines, which are re--acted with methyl chlor acetate or the like to produce thehalogen-containing amides include, among others, by way of example,monoethanolamine, diethainolamine, monopropanolamine, dipropanolamine,mono-butanolamine, dibutanolamine, mono-pentanolamine, dipentanola-.

" No. 219,358, filed July '15, 1938, nowlPatent no,

' mine, mono-hexanolamine, dihexanolamine, ethyl mono-ethanolamine;mono-ethyl ether of diethanolamine; mono-cyclohexyl, beta-hydroxy-ethylamine; N-beta-hydroxyethyl aniline; 2-methylamino-propan-diol-L3;l-phenyl-amino-propandial-2,3; 1-hydroxy-ethylamino-2,methoxy-propanel-3; 2-N methyl amino p'ropan-diol-1,3; monoethanolmonopropanolamine, monoethanol monobutanolamine, glycerol-1,3-propanediol; diglycerol-amine; hydroxylamine (HsN-OH) andderivatives thereof such as result from replacement of one aminehydrogen by an alkyl such as methyl, ethyl, propyl, butyl and the higherhomologues; hydroxy amines, particularly secondary hydroxy amines,derived from polyhydrlc alcohols,v including sugars and mono-amines,namely, 1-amino-2,3-propanediol and 2-aminosugar alcohols such asdextrose, sucrose, sorbitol,

mannitol and dulcitol,

CaH4OH CflEh-NH- clnlon CsHr- 0- cnzn- DE2-amino-2-nl-.-amino-1,1-dimethyl ethanol; trimethylol amino-methylmethane trimethylol 'amino-methylol methane. The glycerol mono-aminesand. the related hydroxy amines such as various of those disclosedhereinabove may be prepared by various procedures and in diflerent ways.Many of them are conveniently produced by nitrating paraffinhydro-carbons, substituting methylol groups for hydrogen on .the carbonsto which the nitro groups are attached, and then reducing the nitroroups to amine groups. These amine groups may be further alkylated orotherwise substituted if desired. "Still other alcohol amines includepolymerized non-tertiary hydroxy amines or polymerized hydroxy aminescontaining hydrogen directly attached to nitrogen and prepared, forexample, by p lymerizing mono-ethanolamine or .diethanolamine ormixtures thereof, or other hydroxy amines such as those mentionedhereinabovaparticularly in the presence of a catalyst such as sodiumhydroxide or the like.- The preparation of polymerized hydroxy amines isdisclosed, for example, in United States Patent No.

2,178,173; and homologues and substitution de-- rivatives oi theabove-mentioned hydroxy amines. As indicated hereinabove, monoetha-'nolamine is especially satisfactory in carrying out the novel processesof the present invention.

Wherever the term "higher" is employed as referring to higher molecularweight organic or fatty acids or the like, it will be understood ctocover compounds or radicals having at least six carbon atoms, unlessotherwise specifically stated.

The present application is a continuationeinpart of .my priorapplication Serial No. 309,575. filed December 16, 1939, which is, inturn, a con-' tinuation-in-part of my prior application Serial whereinwherein 2,184,770, issued December 26, 1939. v

What I claim as new and desire to protect by Letters Patent of theUnited Statesis:

1. Chemical compounds corresponding general formula to the wherein R isa carbox'ylic acyl radical, T and Z a are each members selected from theclass consisting of hydrocarbon-radicals and substitution productsthereof, Y is a member selected from the group consistingnof hydrogen,alkyl, cycloalkyl, alkoxyl; aralkyl, aryl, and alkylol, m and w arewhole numbers, and X is halogen directly attached to carbon of theradical Z. I

2. Chemical compounds corresponding to, the

general formula wherein is an aliphatic acyl radical, Tis a hydrocarbonradical, Y is a memberselected from the group consisting of hydrogen,alkyl,'cycloalkyl, alkoxyl,

'aralkyl, aryl, and alkylol, Z ishydrocarbon, x ishalogen, and w is awhole number.

3. Chemical compounds corresponding to the general formula wherein I v 0Iii is an aliphatic acyl radical,-Y is a member slected from the group.consisting of hydrogen,

alkyl, cycloalkyl, alkoxyl, aralkyl, aryl, and alkylol, and hal ishalogen.

' 4. Chemical compounds corresponding to the general. formula wherein Ris a carbpxylic acyl radical, T is hydrocarbon, Y is a member selectedfrom the is an aliphatic acyl radical, T is hydrocarbon, Y

is a member selected from the group consisting of hydrogen, aikyl,cyclo'allgvl, alkylolf alkoxyl, aralkyl, and aryl Z is hydrocarbon, andhal is halogen. I

6. Chemical compounds corresponding to the general formula l I 3-3 Iisan acyl radical, andhal is halogen.

6 g '7. Chemicalcompounds corresponding to the general formula canon; VR-fil-O-CaHr CO- CHz-hai wherein e-ii. I is an acyl radical, and hal ishalogen.

8. Chemical compounds corresponding general formula to the wherein i atis a fatty acid acyl radical, Y is a member selected from thegroup'consisting of hydrogen, alkyl, cycloalkyl, alkoxyl, aralkyl, aryl,and alkylol, and hal is halogen.

9. Chemical compounds corresponding to the general formula all is analiphatic acyl radical; Y is a member selected from the group consistingof hydrogen, alkyl, cycloalkyl, alkoxyl, aralkyl, aryl, and alkylol, andhal is halogen. g

10. Chemical compounds corresponding to the formula -R-EO-TNYC 0 cHll-hal 11. Chemical compounds corresponding to the formula wherein hal isa member of the group consisting of chlorine and bromine.

12. The process of preparing chemical compounds which comprises reactinga halogenocarboxylic acideamide of an alcohol amine with a memberselected from the. group consisting of carboxylic acids and halidesthereof to form an ester linkage.

13. The process of preparing chemical com-. pounds which comprisesreacting N-beta-hydroxy-ethyl, chloracetamide with an acyl halide toform an ester'linkage.

' 14. The process of preparing chemical compounds which comprisesreacting the methyl ester of chloracetic acid with monoethanolamine attemperatures of about 0 degrees C. to 10 degrees C. to produceessentially N-beta-hydroxyethyl, chloracetamide, then reacting said'amide with acetyl chloride to produce the acetic acidsester of saidamide.

15. The method of preparing chemical compounds which comprises reactinga methyl alcohol ester of a member selected from the group consisting ofchloracetic acid, bromacetic acid, and iodo acetic acid, with a memberselected from the group consisting of primary and secondary.alkylolamines, to form an amide, and then introducing a fatty acid acylradical to form an ester.

16. The method of claim 15 wherein the alkylolamine comprises a memberof the group consisting of monoethanolamine, diethanol- -amine, andmixtures thereof.

17. The method of preparing chemical compounds which comprises reactinga volatile alcohol ester of a halogeno-carboxylic acid with a memberselected from the group consisting of primary and secondary alcoholamines to form an amide, and then introducing into the amide an acylradical to form an ester.

18. The method of preparing chemical compounds which comprises reactinga methyl alcohol ester of a member selected from the group consisting ofchloracetic acid, bromacetic acid and iodo acetic acid, with a memberselected from the group consisting of primary and secondaryalkylolamines to form an amide, said reaction being carried out at atemperature of the order of 0 degrees C. to 10 degrees C., and thenintroducing into said amide a fatty acid acyl radical to form an ester.

, 19. The method of claim 18 wherein the alkylolamine comprises a memberof the group consisting of monoethanolamine, diethanolamine and mixturesthereof.

. 20. The method of preparing chemical compounds which comprisesreacting a volatile al cohol ester of a member selected from the groupconsisting of chloracetic acid, bromacetic acid and iodo acetic acid,with monoethanolamine'at a temperature notabove 10 degrees C. to form anamide of the monoethanolamine, precipitating the excess monoethanolaminewith oxalic acid, filtering to removethe precipitate of monoethanolamineoxalate, distilling the filtrate to remove alcohol formed in theamidiflcation reaction, andreacting the residue with an acyl halide of afatty acid to form an ester.

MORRIS B. KATZMAN.

